Light has profound influences on many non-image forming visual functions (NIFs) including circadian rhythms, sleep, depression and pupillary light reflex. In mammals, light influences these NIFs through three photoreceptor types, namely the classical photoreceptors, rods and cones, and the intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin. As ganglion cells, ipRGCs transmit their own intrinsic light signals and also serve as the sole conduit to signal rod/cone information to brain regions important for these NIFs. However, the functional circuitry by which rods, cones and ipRGCs interact is poorly understood. Emerging evidence suggests that ipRGCs are much more complex than previously appreciated, consisting of multiple morphologically and electrophysiologically distinct subtypes. The functional significance of these different ipRGC subtypes remains unknown. We propose experiments to determine how rods, cones and ipRGCs interact to drive non-image-forming visual functions (Aim I), and to investigate the connectivity and function of the distinct ipRGC subtypes (Aim II and III). These studies will allow better understanding of the circuitry and physiological outcome of light effects on behaviors. This is of prime importance because light and the circadian clock temporally regulate many physiological parameters that influence sleep, depression, and general health in humans. PUBLIC HEALTH RELEVANCE: In mammals, circadian photoentrainment is responsible for synchronizing many physiological rhythms to the solar day. Disruption of the regular 24-hour light/dark cycle, which can occur in shift work or jet-lag, leads to de-synchronization of the body's internal circadian clock from the solar day. Such de-synchrony is detrimental to human health not only causing sleep disorders, but is has also been implicated in many diseases ranging from depression to breast cancer.